The metabolism of hemoglobin and its heme moiety are under investigation. In particular, we are studying the function of serum proteins in the transport and catabolism of heme and heme metabolities. Hemopexin, a serum Beta-glycoprotein, functions in the selective transport of intravascular heme to the liver parenchymal cell and thus plays a role in conserving biologically available iron as well as in preventing toxic effects of heme. On-going studies have provided much information, but several important questions remain. How does the heme-hemopexin complex interact with the hepatocyte? What is the fate of the complex at the liver cell? What is the nature of the recognition site on the membrane for the complex? We plan to study hemopexin's function in heme metabolism at several levels. First, we will characterize the interaction of heme-hemopexin with liver cells and liver cell membranes. Second, we will study the fate of heme and hemopexin subsequent to their entering the liver cell, with particular emphasis on the role of subcellular organelles like lysosomes in determining that fate. Third, we will continue to assess the clinical diagnostic usefulness of serum hemopexin levels and to investigate the metabolism of hemopexin in hemolytic and other disease states in which heme metabolism is altered. Fourth, we will continue to define the physical-chemical characteristics of the hemopexin molecule and its interaction with heme to provide basic information required for full understanding of this protein's function in heme transport. The heme-hemopexin-liver cell system may be an informative model of serum transport protein-ligand-cell interactions because of the specificity of the equimolar interaction of hemopexin with liver, the information available on the chemistry and biology of hemopexin, and its analogy with other serum transport processes. Rational approaches to the clinical treatment of several disease states, such as certain vitamin deficiencies and abnormal hormone responses, requires detailed knowledge of the mechanism of action of serum transport proteins.